A culture of the microorganism, designated Nocardia sp. ATCC 39043, directly produces erythromycin D by fermentation, together with esters comprising 4"-O-acetylerythromycin D, 3",4"-di-O-acetylerythromycin D and 3"-O-acetyl-4"-O-propionylerythromycin D. The most valuable of these esters, the 3",4"-diacetate, is the major component of the fermentation. If erythromycin D itself is the desired product, hydrolysis of the esters is optionally carried out in the broth prior to isolation of the erythromycin D.
Erythromycin D is one of a group of macrolide antibiotics having common structural characteristics as follows:
______________________________________ ##STR1## R.sup.a R.sup.b ______________________________________ Erythromycin A OH CH.sub.3 Erythromycin B H CH.sub.3 Erythromycin C OH H Erythromycin D H H ______________________________________
Majer et al., J. Am. Chem. Soc., 99, pp. 1620-1622, (1977), isolated and identified erythromycin D as a trace component from an industrial erythromycin A purification side stream. The present invention provides a practical preparation of erythromycin D by direct fermentation.
Previously reported esters in the erythromycin series were made by chemical methods, not as fermentation products. These esters include the 2'-acetate, the 2'-propionate, the 4"-acetate and the 4"-propionate esters of both erythromycin A and erythromycin B. See Jones et al., J. Med. Chem. 15, pp. 631-634 (1972); Martin et al., J. Med. Chem., 15 pp. 635-637 (1972).
Structurally related esters have been previously reported as part of the megalomicin complex of antibiotics. Megalomicin A, having a third sugar moiety attached at C-6, otherwise corresponds in structure to erythromycin C. Other members of this series are esters of megalomicin A, as follows:
______________________________________ ##STR2## ##STR3## R.sup.d R.sup.e ______________________________________ Megalomicin A H H Megalomicin B COCH.sub.3 H Megalomicin C.sub.1 COCH.sub.3 COCH.sub.3 Megalomicin C.sub.2 COC.sub.2 H.sub.5 COCH.sub.3 ______________________________________
See Bartner et al., J. Chem. Soc., Perkin I, pp. 1600-1624 (1979).